Neuroactive steroid for the treatment of alzheimer's disease

Abstract

The present disclosure relates to compositions, kits and methods of treating Alzheimer's disease comprising administering an NMD A receptor positive allosteric modulator or a CYP46A1 inhibitor.

1 . A method of:
 a) treating Mild Cognitive Impairment (MCI) associated with Alzheimer's Disease in a subject;   b) improving executive function in a subject having MCI associated with Alzheimer's Disease;   c) improving working memory in a subject having MCI associated with Alzheimer's Disease;   d) improving learning in a subject having MCI associated with Alzheimer's Disease;   comprising administering to the subject a compound having the formula   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 .- 5 . (canceled) 
     
     
         6 . A method of:
 a) treating mild dementia associated with Alzheimer's Disease in a subject;   b) improving executive function in a subject having mild dementia associated with Alzheimer's Disease;   c) improving working memory in a subject having mild dementia associated with Alzheimer's Disease;   d) improving learning in a subject having mild dementia associated with Alzheimer's Disease;   comprising administering to the subject a compound having the formula   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         7 .- 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein about 3 mg daily of Compound 1 is administered to the subject. 
     
     
         14 .- 36 . (canceled) 
     
     
         37 . A pharmaceutical composition comprising:
 (1) (a) an NMDA receptor positive allosteric modulator;   (b) an anti-amyloid beta antibody or antigen-binding fragment thereof, and   (c) a pharmaceutically acceptable carrier; or   (2) (a) a CYP46A1 inhibitor;   (b) an anti-amyloid beta antibody or antigen-binding fragment thereof; and   (c) a pharmaceutically acceptable carrier.   
     
     
         38 .- 50 . (canceled) 
     
     
         51 . A kit comprising
 (1) a first container, a second container and a package insert, wherein:
 the first container comprises a composition comprising an NMDA receptor positive allosteric modulator; 
 the second container comprises composition comprising an anti-amyloid beta antibody or antigen-binding fragment thereof; and 
 the package insert comprises instructions for treating Alzheimer's disease in a subject; or 
   (2) a first container, a second container and a package insert, wherein:
 the first container comprises a composition comprising CYP46A1 inhibitor; 
 the second container comprises composition comprising an anti-amyloid beta antibody or antigen-binding fragment thereof; and 
 the package insert comprises instructions for treating Alzheimer's disease in a subject. 
   
     
     
         52 . (canceled) 
     
     
         53 . A method for treating or preventing Alzheimer's disease, comprising administering to a subject in need thereof a pharmaceutical composition according to  claim 37 . 
     
     
         54 . A method for treating or preventing cognitive impairment in a subject having Alzheimer's disease, comprising administering to the subject a pharmaceutical composition according to  claim 37 . 
     
     
         55 .- 100 . (canceled)